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BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these supra-modal traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a general response pattern factor for each supra-modal construct and determine the added value of modality-specific response pattern scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many real-world sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Background: Existing evidence indicates that atypical sensory reactivity is a core characteristic of autism, and has been linked to both anxiety (and its putative infant precursor of fearfulness) and repetitive behaviours. However, most work has used cross‐sectional designs and not considered the differential roles of hyperreactivity and hyporeactivity to sensory inputs, and is thus limited in specificity. Methods: 161 infants with and without an elevated likelihood of developing autism and attention‐deficit hyperactivity disorder (ADHD) were followed from 10 to 36 months of age. Parents rated an infant precursor of later anxiety (fearfulness) using the Infant Behaviour Questionnaire at 10 and 14 months, and the Early Childhood Behavioural Questionnaire at 24 months, and sensory hyperreactivity and hyporeactivity at 10, 14 and 24 months using the Infant Toddler Sensory Profile. Domains of autistic traits (restrictive and repetitive behaviours; RRB, and social communication interaction, SCI) were assessed using the parent‐rated Social Responsiveness Scale at 36 months. Cross‐lagged models tested (a) paths between fearfulness and hyperreactivity at 10–24 months, and from fearfulness and hyperreactivity to later autism traits, (b) the specificity of hyperreactivity effects by including hyporeactivity as a correlated predictor. Results: Hyperreactivity at 14 months was positively associated with fearfulness at 24 months, and hyperreactivity at 24 months was positively associated with SCI and RRB at 36 months. When hyporeactivity was included in the model, paths between hyperreactivity and fearfulness remained, but paths between hyperreactivity and autistic traits became nonsignificant. Conclusions: Our findings indicate that alterations in early sensory reactivity may increase the likelihood of showing fearfulness in infancy, and relate to later social interactions and repetitive behaviours, particularly in individuals with a family history of autism or ADHD. [ABSTRACT FROM AUTHOR]

Abstract Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these “supra-modal” traits in the autistic population. Methods Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3–18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a “general response pattern” factor for each supra-modal construct and determine the added value of “modality-specific response pattern” scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). Limitations Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many “real-world” sensory experiences. Conclusion Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Introduction and Methods: This study examined 85 parental‐reports with 85 self‐reports of autistic symptoms with the 84‐item Coolidge Autistic Symptom Survey (CASS). The CASS covers all of the diagnostic criteria for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5), as no studies to date have compared the self‐reports of individuals with autism with parent‐ or significant‐other‐reports of those individuals using the complete DSM‐5. Results: The CASS‐Parental‐Report and CASS‐Self‐Report exhibited excellent internal reliability (α = 0.97 and 0.96, respectively). There was support for the hypothesis that parental‐reports and self‐reports would be similar (r = 0.66, p < 0.001). Discussion: In conclusion, the CASS should be considered a promising tool for assessing autistic symptoms from both parent‐ and self‐perspectives. [ABSTRACT FROM AUTHOR]

Background: Sensory processing issues are among the key diagnostic criteria for autism spectrum disorder (ASD). As altered sensory processing causes autistic children to react differently to sensory experiences and has a profound impact on their development, affecting their learning ability, social interaction, and ability to adapt to a new environment, there is a need to recognize and address these issues in children diagnosed with ASD during assessments and interventions. This study aimed to identify the patterns of sensory issues and their impact, and selected correlates among autistic children attending a center for neurodevelopmental disorders in northern Sri Lanka., Methods: This institution-based, descriptive, cross-sectional study was conducted at a center for neurodevelopmental disorders in Jaffna among 100 children diagnosed with ASD. The sociodemographic details of the child, and scores of the Childhood Autism Rating Scale second edition (CARS™ 2), Sensory Profile™ 2, and a locally developed Behavioral Checklist were extracted from the records available at the center. Data were analyzed using R statistical computing software (R Foundation for Statistical Computing, Vienna, Austria) using general linear models., Results: All the children in this study had at least one sensory issue, with 50% having visual processing issues. The severity of ASD increased as auditory processing issues increased. Behavioral issues, in general, increased significantly with increasing auditory and visual processing issues. Repetitive behaviors significantly increased with increasing auditory processing issues, while problems with self-regulation increased significantly with increasing visual and movement processing issues. Conduct-related issues were found to increase significantly with increasing movement and visual processing issues, and attentional response issues were found to increase significantly with increasing auditory, visual, and touch processing issues., Conclusion: The high prevalence of sensory issues in autistic children and its impact on the severity of ASD and behavioral issues are reiterated in this study. These results emphasize the importance of including interventions targeting sensory issues with the routine therapy for ASD., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Review Committee of the Faculty of Medicine, University of Jaffna issued approval J/ERC/22/143/NDR/0285. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sivapalan et al.)

We evaluated the effects of phenylephrine, norepinephrine, angiotensin II, and vasopressin in mesenteric, renal, carotid, and tail arteries, and in perfused mesenteric vascular bed from rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Phenylephrine and angiotensin II were less efficacious in mesenteric arteries from the CLP 6 h and CLP 18 h groups than in preparations from non-septic animals, but no differences were found for norepinephrine and vasopressin between the preparations. In renal arteries, none of the vasoconstrictors had impaired activity in the CLP groups. Nonetheless, carotid arteries from the CLP 18 h group presented reduced reactivity to all vasoconstrictors tested, but only phenylephrine and norepinephrine had their effects reduced in carotid arteries from the CLP 6 h group. Despite the reduced responsiveness to phenylephrine, tail arteries from septic rats were hyperreactive to vasopressin and norepinephrine at 6 h and 18 h after the CLP surgery, respectively. The mesenteric vascular bed from CLP groups was hyporeactive to phenylephrine, norepinephrine, and angiotensin II, but not to vasopressin. The vascular contractility in sepsis varies from the well-described refractoriness, to unaltered or even hyperresponsiveness to vasoconstrictors, depending on the vessel, the vasoactive agent, and the time period evaluated. [ABSTRACT FROM AUTHOR]

Aims We determined whether decreased reactive oxygen species (ROS) production in the aorta of pregnant spontaneously hypertensive rats (SHR) resulted in increased nitric oxide (NO) bioavailability and hyporeactivity to phenylephrine (PE). Main methods Systemic and aortic oxidative stress were measured in pregnant and non-pregnant Wistar rats and SHR. Furthermore, the hypotensive effects of apocynin (30 mg/kg) and Tempol (30 mg/kg) were analyzed. Intact aortic rings of pregnant and non-pregnant rats were stimulated with PE in the absence of or after incubation (30 min) with apocynin (100 μmol/L). The effect of apocynin on the concentrations of NO and ROS were measured in aortic endothelial cells (AEC) using DAF-2DA (10 mmol/L) and DHE (2.5 mmol/L), respectively. Western blotting was performed to analyze eNOS, NOX1, NOX2, NOX4 and SOD expression. ROS production was analyzed by the lucigenin chemiluminescence method. Key findings Aortic oxidative stress and ROS concentration in AEC were reduced in pregnant Wistar rats and SHR, when compared to non-pregnant rats. ROS production and NOX1, NOX2 and NOX4 expression in the aortas were decreased in pregnant SHR, but not in pregnant Wistar rats. Increased eNOS expression in aortas and NO concentration in AEC were observed in pregnant Wistar rats and SHR. Apocynin reduced PE-induced vasoconstriction in the aortas of non-pregnant Wistar rats and SHR, and pregnant Wistar rats, but not in the aortas of pregnant SHR. Significance Taken together, these results suggest that ROS production was decreased in the aortas of pregnant SHR and could contribute to higher NO bioavailability and hyporeactivity to PE in the aortas of pregnant SHR. [ABSTRACT FROM AUTHOR]

Irritant contact dermatitis (ICD) is common and poses a significant problem in high-risk populations. In most cases, ICD resolves despite continued exposure in a process known as ‘hardening’, allowing individuals to continue with their work. Those who cannot clear ICD develop chronic ICD, which is a significant source of emotional, physical, and financial distress for affected individuals. While hardening is well known among labourers and clinicians, its mechanism remains to be elucidated. Much can be learned from the study of self-healing processes like the hardening phenomenon. This overview briefly documents the pathogenesis of ICD, focuses on the latest advances pertaining to the hardening phenomenon in ICD, and then highlights potential avenues of productive research. A better understanding of the ‘hardening’ process in the skin will hopefully lead to advances for the treatment of ICD. [ABSTRACT FROM AUTHOR]

Melatonin (MT) is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that MT exerts protective effects in septic shock, hemorrhagic shock and inflammation. Lipopolysaccharide (LPS), from Escherichia coli, administered to animals directly stimulates a number of cells and systems to produce various inflammatory mediators. LPS-induced septic shock is characterized by hypotension and vascular hyporeactivity to contracting agents. In particular, the reactive oxygen species such as superoxide and nitric oxide (NO) contribute to the pathophysiology of septic shock. In this study, we demonstrate that MT pretreatment prevents the hyporeactivity to phenylephrine in vivo and in aorta rings collected from rats treated with the endotoxin. The beneficial effect of MT seems related to its antioxidant properties and with inhibition of inducible nitric oxide synthase (iNOS) protein expression, reduction of NO production and nitrotyrosine formation, in aorta, preventing vascular, and endothelial injury. Additionally, we first demonstrate, that MT inhibited nuclear enzyme poly (ADP-ribose) synthetase activation in vascular tissue. The current study underlined the protective effect of MT on the vascular dysfunction associated with septic shock, data that could support the clinical use of MT in human endotoxemia. [ABSTRACT FROM AUTHOR]

Peroxynitrite (ONOO−) has been recently known to act as a potent cytotoxin during pathogenesis of various diseases. This study aimed to investigate the possible effect of ONOO− on the cremaster muscle arteriolar reactivity in response to noradrenaline and subsequently determined whether membrane hyperpolarization and potassium channel activation were involved in ONOO−-induced alteration of arteriolar reactivity. The results demonstrated that 1) ONOO− could decrease arteriolar reactivity in a time- and concentration-dependent manner with no significant alteration of arteriolar diameter; 2) Superfusion with 20 μM ONOO− over 40 minutes showed slight but not significant influence on the resting potential (Em) of arteriolar smooth muscle cells (ASMCs). However, ASMCs subjected to 50 or 100 μM ONOO− administration were significantly hyperpolarized. As control, treatment with 50 μM decomposed ONOO− or Kreb''s solution had little effect on the Em of ASMCs; 3) ONOO−-induced arteriolar hyporeactivity could be greatly reversed by co-administration of KCl and partially by TEA. The above results indicated that membrane hyperpolarization and potassium channel activation were preferentially responsible for the reduction of cremaster muscle arteriolar reactivity after exposure to ONOO−. [Copyright &y& Elsevier]

Objective: Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents. Methods: In phenobarbital-anaesthetised rats hypotension was induced by graded haemorrhage (8 ml blood total). Sham-manipulated rats served as controls. Blood flow (BF) was recorded with ultrasonic transit time flow probes. Results: Following haemorrhage mean arterial pressure (MAP) fell by 25–45 mm Hg and was accompanied by a reduction in mesenteric BF without any alteration of mesenteric vascular conductance (VC). While pressor responses to arginine vasopressin remained unaltered, hyporesponsiveness to phenylephrine (10 nmol kg−1) developed 120–180 min after hypotension had been induced. Pressor and mesenteric constrictor responses to angiotensin II (30 pmol kg−1) became significantly blunted as early as 60 min post haemorrhage. The hypotensive effect of an angiotensin1 receptor antagonist, telmisartan (1 mg kg−1), was likewise blunted 3 h after haemorrhage. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg kg−1) exaggerated the hypotensive reaction to haemorrhage but did not prevent the development of angiotensin II hyporesponsiveness. In contrast, the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (10 mg kg−1), as investigated 3 h post haemorrhage, restored the systemic pressor responses to angiotensin II and phenylephrine as well as the mesenteric constrictor responses to phenylephrine to normal level and diminished the mesenteric hyporesponsiveness to angiotensin II. Glibenclamide (20 mg kg−1), an inhibitor of ATP-sensitive K+ channels given 180 min post haemorrhage, partially reversed haemorrhage-induced hypotension but did not modify angiotensin II hyporesponsiveness. Conclusion: Systemic pressor responsiveness and mesenteric arterial reactivity to endogenous and exogenous angiotensin II is selectively impaired at an early stage of haemorrhagic hypotension. This phenomenon partially involves NO and is not related to ATP-sensitive K+ channels. [ABSTRACT FROM PUBLISHER]